Molecular Characterization of Hereditary Persistence of Fetal Hemoglobin in the Karen People of Thailand

• Published in: Hemoglobin 2003-01, Vol.27 (2), p.97-104
• Main Authors: Trachoo, Objoon, Sura, Thanyachai, Sakuntabhai, Anavaj, Singhasivanon, Pratap, Krudsood, Srivicha, Phimpraphi, Waraphon, Krasaesub, Somporn, Chanjarunee, Suporn, Looareesuwan, Sornchai
• Format: Article
• Language: English
• Subjects: Adult; Asian Continental Ancestry Group; Base Sequence; beta-Thalassemia - genetics; Deletional thalassemias; DNA Primers; Ethnic Groups; Female; Fetal Hemoglobin - genetics; Globins - genetics; Hereditary persistence of fetal hemoglobin (HPFH); Heterozygote; Humans; Karen; Molecular Sequence Data; Polymerase Chain Reaction - methods; Reference Values; Sequence Deletion; Thailand; β-Globin gene cluster
• ISSN: 0363-0269; 1532-432X
• DOI: 10.1081/HEM-120021542

Hereditary persistence of fetal hemoglobin (HPFH) is the condition whereby a continuously active γ-globin gene expression leads to elevated fetal hemoglobin (Hb F) levels in adult life [Stamatoyannopoulos G, Grosveld F. Hemoglobin switching. In: Stamatoyannopoulos G, Majerus PW, Perlmutter RM, Varmus H, eds. The Molecular Basis of Blood Diseases. Philadelphia: W.B. Saunders, 2001:135-182; Wood WG. Hereditary persistence of fetal hemoglobin and δβ thalassemia. In: Steinberg MH, Forget BG, Higgs DR, Nagel RL, eds. Disorders of Hemoglobin: Genetics, Pathophysiology, and Clinical Management. Cambridge: Cambridge University Press, 2001:356-388; and Weatherall DJ, Clegg JB. Hereditary persistence of fetal hemoglobin. In: Weatherall DJ, Clegg JB, eds. The Thalassaemia Syndromes. Oxford: Blackwell Scientific Publishers, 1981:450-507]. The condition is caused either by mutation of the β- and γ-globin genes, or the γ-gene controlled region on other chromosomes. Several families with this condition have been reported from Vietnam, Cambodia and China, and the Southeast Asian mutation (or HPFH-6), a 27 kb deletion, was demonstrated. Here we report on a mother and her daughter of the Karen ethnic group with high levels of Hb F, living in the Suan Pueng District on the border of Thailand and Myanmar. Genotyping showed a heterozygosity for the 27 kb deletion of the β-globin gene. Their conditions have been confirmed by gap polymerase chain reaction (PCR) with three oligonucleotide primers recently developed by Xu et al. [Xu X-M, Li Z-Q, Liu Z-Y, Zhong X-L, Zhao Y-Z, Mo Q-H. Molecular characterization and PCR detection of a deletional HPFH: application to rapid prenatal diagnosis for compound heterozygotes of this defect with β-thalassemia in a Chinese family. Am J Hematol 2000; 65:183-188.], and a DNA sequencing method. Thus far there has been no official report of the HPFH-6 anomaly from Thailand. The compound heterozygosity of β-thalassemia (thal) and hereditary persistence of Hb F causes the phenotype of thalassemia intermedia; in contrast, homozygotes for this anomaly show only mild microcytic anemia. Hence, genetic counseling for hereditary persistence of Hb F carriers is needed for family planning.